E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Kidney Disease (CKD) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To study the effects of once daily oral dosing of sitaxsentan 100 mg tablets over a period of 6 weeks on proteinuria, systemic blood pressure (BP) measured by 24-hour ambulatory BP monitoring, and arterial stiffness as measured by pulse wave velocity (PWV) in subjects with chronic kidney disease (CKD).
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A substudy will evaluate the effects of once daily oral dosing of sitaxsentan 100 mg tablets over a period of 6 weeks on renal and systemic haemodynamics. |
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E.3 | Principal inclusion criteria |
1. Has stage 1-5 chronic kidney disease (CKD) as defined by the kidney disease Outcomes Quality Initiative (K/DOQI) (using a 24 hour urine collection for creatinine clearance to estimate glomerular filtration rate(GFR)) with proteinuria, including any of the following aetiologies: immunoglobulin A (IgA) nephropathy, polycystic kidney disease (PCKD), congenital abnormalities, reflux nephropathy, focal segmental glomerulosclerosis, minimal change nephropathy and membranous nephropathy. 2. Between 18 and 70 years of age, inclusive. 3. Has a body mass index (BMI) between 18 and 35 kg/m2, inclusive. 4. Is willing and able to adhere to the protocol requirements. 5. Provides written informed consent before any study procedure is performed.
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E.4 | Principal exclusion criteria |
1. Requires peritoneal dialysis or haemodialysis. 2. Has kidney disease due to diabetes mellitus, vasculitis, systemic lupus membrane erythematosus, or known renovasular disease; antiglomerular basement membrane disease; or is on immunosuppressive medication. 3. Has a serum albumin in the nephritic range (<30 g/L) during Screening. 4. Has a sustained sitting systolic blood pressure (BP)> 160 mmHg or sustained sitting diastolic BP > 100 mmHg during screening. 5. Has a postural hypotension during screening which is defined as a decrease in systolic BP ≥20 mmHg and/or a decrease in diastolic BP ≥10 mmHg, comparing sitting and standing measurements. 6. Has a history and/or evidence of ischaemic heart disease. 7. Has or had a malignancy, with the exception of adequately-treated basal cell or squamous cell carcinoma of the skin that required significant medical intervention within the past 3 months and/or is likely to result in death within the next 2 years. 8. Has a history of allergies or hypersensitivity to sitaxentan or nifedipine or the excipients of either drug. 9. Has clinically significant psychiatric, addictive, neurological disease or any other condition that, in the Investigator’s opinion, would compromise his/her ability to give informed consent, participate fully in this study, prevent adherence to the requirements of the study protocol, or would compromise the interpretation of the data obtained from this study. 10. Uses a prohibited medication or plans to use a prohibited medication during the study. Prohibited medications include cyclosporine A, alternative endothelin (ET) receptor antagonist,phosphodiesterase inhibitors, and/or vitamin K antagonist (e.g warfarin). The intermittent use of phosphodiesterase inhibitors (e.g sildenafil) "as needed” for erectile dysfunction is acceptable, however, as long as the subject is not dosed within 24 hours of an efficacy assessment. 11. Received treatment with an investigational drug or device within 30 days prior to study entry. 12. Has a history of organ transplantation. 13. Has atrial fibrillation requiring anticoagulation or a history (in the preceding 6 months) of any intermittent cardiac dysrhythmia that may require anticoagulation therapy. 14. Has an alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) level >1.5 x the upper limit of the normal range (ULN) at screening and/or serum total bilirubin > ULN 15. Has a haemoglobin concentration <8.0 mg/dL at screening. 16. Has a positive serological results for hepatitis B and/or hepatitis C. 17. Is a woman of childbearing potential who is willing to use 2 forms of contraceptive therapy, including at least 1 barrier method, throughout the study. (Women who are surgically sterile or who are post-menopausal for at least 2 years are not considered to be of childbearing potential.) 18. Is pregnant, lactating, or breastfeeding 19. Has, in the opinion of the investigator, a dependence on alcohol 20. Has, in the opinion of the investigator, a dependence on illicit drugs.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point is a statistically significant reduction in proteinuria as measured by 24-hour urine collections at the week 6 visit a compared to baseline/Day 1 in each treatment period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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On completion of the end of study assessment (two weeks following completion of treatment period 3) of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |